For decades, liver cancer is always the second most common main cause of death induced by cancer all over the world, and there are about 750 thousand new cases each year. Furthermore, morbidity and mortality of liver cancer have a tendency to increase year by year, and health and life of Chinese and even global people are seriously threatened. High incidence of morbidity and mortality of liver cancer mainly attribute to later diagnosis and limited available treatment methods for the disease. In addition, surgical treatment is not suitable for most of patients due to lack of available transplantation donors. Thus, it is urgent to develop a new liver cancer treatment strategy. Prosperous development of a nano technology can well overcome disadvantages existing in the current liver cancer treatment. Since physical and chemical properties of the nano material can be precisely improved through regulation of chemical components, size, shape, structure, morphology, surface modification and the like, the nano material can be used as a potential carrier for co-delivery of nucleic acid substances and drugs to be used for liver cancer treatment. However, due to the defects of immunogenicity, low transfection efficiency, toxic or side effects and the like of the present nano material, its development of clinical application is hindered. In addition, due to complexity of intrahepatic and extrahepatic metastasis of liver cancer, the present nano material for liver cancer treatment is far from enough in the aspect of study on an in vivo treatment effect in a subcutaneous solid tumor mouse model.
In recent years, a cationic polymer poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) has been largely used as a stable complex formed by loading nucleic acid with negative charges to be used for gene therapy as containing a large amount of amino groups. Under the acidic condition, a sponge effect can be triggered to cause escape of an inclusion body, so as to perform gene transfection. Moreover, this polymer can easily form a copolymer with other hydrophobic fragments via a free radical polymerization technology, and the hydrophobic drug is coated in the hydrophobic fragments through hydrophilic and hydrophobic interaction. These advantages allow combination of PDMAEMA and other polymers to become an ideal carrier for achieving co-delivery of nucleic acid for liver cancer treatment and an anti-cancer drug. For liver-targeting recognition, the ligand, since the surfaces of liver cells are overexpresed with an asialoglycoprotein receptor (ASGPR), can be specifically recognized, thereby reducing toxic or side effects. Because of low price, wide source, easy modification and other features, galactose has been widely used for modifying nano materials and applied to study on in vitro and in vivo (subcutaneous solid tumor mouse model) anti-tumor effects of specifically targeted human hepatoma cells. In addition, introduction of a fluorescence label into a nano system can render the nano material to be monitored in real time in vivo, thereby improving the potential for clinical diagnosis and treatment.
Although there have been many related studies for obtaining a nano material capable of achieving co-delivery of nucleic acid and an anti-cancer drug, these systems for liver cancer treatment have not been sufficiently utilized yet. And there is no report about introduction of a tracing molecule and a targeting molecule into a co-delivery carrier of nucleic acid having a stimulating response function and the anti-cancer drug. It is still a challenge that multiple functions are integrated into the same nano carrier to be used for liver cancer targeting treatment.